Search results for: Mikhail Panes

Authors: Alla Ovsyannikova, Oksana Rymar, Elena Shakhtshneider, Mikhail Voevoda

Abstract:

In Siberia endocrinologists increasingly noted young patients with the course of diabetes mellitus differing from 1 and 2 types. Therefore we did a molecular genetic study for this group of patients to verify the monogenic forms of diabetes mellitus in them and researched the characteristics of this pathology. When confirming the monogenic form of diabetes, we performed a correction therapy for many patients (transfer from insulin to tablets), prevented specific complications, examined relatives and diagnosed their diabetes at the preclinical stage, revealed phenotypic characteristics of the pathology which led to the high significance of this work. Materials and Methods: We observed 5 patients (4 families). We diagnosed MODY (Maturity Onset Diabetes of the Young) during the molecular genetic testing (direct automatic sequencing). All patients had a full clinical examination, blood samples for biochemical research, determination of C-peptide and TSH, antibodies to b-cells, microalbuminuria, abdominal ultrasound, heart and thyroid ultrasound, examination of ophthalmologist. Results: We diagnosed 3 rare types of MODY: two women had MODY8, one man – MODY6 and man and his mother - MODY12. Patients with types 8 and 12 had clinical features. Age of onset hyperglycemia ranged from 26 to 34 years. In a patient with MODY6 fasting hyperglycemia was detected during a routine examination. Clinical symptoms, complications were not diagnosed. The patient observes a diet. In the first patient MODY8 was detected during first pregnancy, she had itchy skin and mostly postprandial hyperglycemia. Upon examination we determined glycated hemoglobin 7.5%, retinopathy, non-proliferative stage, peripheral neuropathy. She uses a basic bolus insulin therapy. The second patient with MODY8 also had clinical manifestations of hyperglycemia (pruritus, thirst), postprandial hyperglycemia and diabetic nephropathy, a stage of microalbuminuria. The patient was diagnosed autoimmune thyroiditis. She used inhibitors of DPP-4. The patient with MODY12 had an aggressive course. In the detection of hyperglycemia he had complaints of visual impairment, intense headaches, leg cramps. The patient had a history of childhood convulsive seizures of non-epileptic genesis, without organic pathology, which themselves were stopped at the age of 12 years. When we diagnosed diabetes a patient was 28 years, he had hypertriglyceridemia, atherosclerotic plaque in the carotid artery, proliferative retinopathy (lacerocoagulation). Diabetes and early myocardial infarction were observed in three cases in family. We prescribe therapy with sulfonylureas and SGLT-2 inhibitors with a positive effect. At the patient's mother diabetes began at a later age (30 years) and a less aggressive course was observed. She also has hypertriglyceridemia and uses oral hypoglycemic drugs. Conclusions: 1) When young patients with hyperglycemia have extrapancreatic pathologies and diabetic complications with a short duration of diabetes we can assume they have one of type of MODY diabetes. 2) In patients with monogenic forms of diabetes mellitus, the clinical manifestations of hyperglycemia in each succeeding generation are revealed at an earlier age. Research had increased our knowledge of the monogenic forms of diabetes. The reported study was supported by RSCF, research project No. 14-15-00496-P.

Keywords: diabetes mellitus, MODY diabetes, monogenic forms, young patients

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Authors: Inas Raafat, Azza El Bassiouny, Waldemar L. Olszewsky, Nagui E. Mikhail, Mona Nossier, Nora E. I. El-Bassiouni, Mona Zoheiry, Houda Abou Taleb, Noha Abd El-Aal, Ali Baioumy, Shimaa Attia

Abstract:

Background: Orthotopic liver transplantation is an established treatment for patients with severe acute and end-stage chronic liver disease. The shortage of donor organs continues to be the rate-limiting factor for liver transplantation throughout the world. Hepatocyte transplantation is a promising treatment for several liver diseases and can, also, be used as a "bridge" to liver transplantation in cases of liver failure. Aim of the work: This study was designed to develop a highly efficient protocol for isolation and transplantation of hepatocytes in experimental Lewis rat model to provide satisfactory guidelines for future application on humans.Materials and Methods: Hepatocytes were isolated from the liver by double perfusion technique and bone marrow cells were isolated by centrifugation of shafts of tibia and femur of donor Lewis rats. Recipient rats were subjected to sub-lethal dose of irradiation 2 days before transplantation. In a laparotomy operation the spleen was injected by freshly isolated hepatocytes and bone marrow cells were injected intravenously. The animals were sacrificed 45 day latter and splenic sections were prepared and stained with H & E, PAS AFP and Prox1. Results: The data obtained from this study showed that the double perfusion technique is successful in separation of hepatocytes regarding cell number and viability. Also the method used for bone marrow cells separation gave excellent results regarding cell number and viability. Intrasplenic engraftment of hepatocytes and live tissue formation within the splenic tissue were found in 70% of cases. Hematoxylin and eosin stained splenic sections from 7 rats showed sheets and clusters of cells among the splenic tissues. Periodic Acid Schiff stained splenic sections from 7 rats showed clusters of hepatocytes with intensely stained pink cytoplasmic granules denoting the presence of glycogen. Splenic sections from 7 rats stained with anti-α-fetoprotein antibody showed brownish cytoplasmic staining of the hepatocytes denoting positive expression of AFP. Splenic sections from 7 rats stained with anti-Prox1 showed brownish nuclear staining of the hepatocytes denoting positive expression of Prox1 gene on these cells. Also, positive expression of Prox1 gene was detected on lymphocytes aggregations in the spleens. Conclusions: Isolation of liver cells by double perfusion technique using collagenase buffer is a reliable method that has a very satisfactory yield regarding cell number and viability. The intrasplenic route of transplantation of the freshly isolated liver cells in an immunocompromised model was found to give good results regarding cell engraftment and tissue formation. Further studies are needed to assess function of engrafted hepatocytes by measuring prothrombin time, serum albumin and bilirubin levels.

Keywords: Lewis rats, hepatocytes, BMCs, transplantation, AFP, Prox1

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Authors: Irina Mizeva, Elena Potapova, Viktor Dremin, Mikhail Mezentsev, Valeri Shupletsov

Abstract:

The local tissue perfusion is regulated by the microvascular tone which is under the control of a number of physiological mechanisms. Laser Doppler flowmetry (LDF) together with wavelet analyses is the most commonly used technique to study the regulatory mechanisms of cutaneous microcirculation. External factors such as temperature, local pressure of the probe on the skin, etc. influence on the blood flow characteristics and are used as physiological tests to evaluate microvascular regulatory mechanisms. Local probe pressure influences on the microcirculation parameters measured by optical methods: diffuse reflectance spectroscopy, fluorescence spectroscopy, and LDF. Therefore, further study of probe pressure effects can be useful to improve the reliability of optical measurement. During pressure tests variation of the mean perfusion measured by means of LDF usually is estimated. An additional information concerning the physiological mechanisms of the vascular tone regulation system in response to local pressure can be obtained using spectral analyses of LDF samples. The aim of the present work was to develop protocol and algorithm of data processing appropriate for study physiological response to the local pressure test. Involving 6 subjects (20±2 years) and providing 5 measurements for every subject we estimated intersubject and-inter group variability of response of both averaged and oscillating parts of the LDF sample on external surface pressure. The final purpose of the work was to find special features which further can be used in wider clinic studies. The cutaneous perfusion measurements were carried out by LAKK-02 (SPE LAZMA Ltd., Russia), the skin loading was provided by the originally designed device which allows one to distribute the pressure around the LDF probe. The probe was installed on the dorsal part of the distal finger of the index figure. We collected measurements continuously for one hour and varied loading from 0 to 180mmHg stepwise with a step duration of 10 minutes. Further, we post-processed the samples using the wavelet transform and traced the energy of oscillations in five frequency bands over time. Weak loading leads to pressure-induced vasodilation, so one should take into account that the perfusion measured under pressure conditions will be overestimated. On the other hand, we revealed a decrease in endothelial associated fluctuations. Further loading (88 mmHg) induces amplification of pulsations in all frequency bands. We assume that such loading leads to a higher number of closed capillaries, higher input of arterioles in the LDF signal and as a consequence more vivid oscillations which mainly are formed in arterioles. External pressure higher than 144 mmHg leads to the decrease of oscillating components, after removing the loading very rapid restore of the tissue perfusion takes place. In this work, we have demonstrated that local skin loading influence on the microcirculation parameters measured by optic technique; this should be taken into account while developing portable electronic devices. The proposed protocol of local loading allows one to evaluate PIV as far as to trace dynamic of blood flow oscillations. This study was supported by the Russian Science Foundation under project N 18-15-00201.

Keywords: blood microcirculation, laser Doppler flowmetry, pressure-induced vasodilation, wavelet analyses blood

Procedia PDF Downloads 150